Absence of proline cis-conformation in poly-proline tracts

The study of prolines within proteins has been traditionally a challenge, especially in repetitions (poly-proline). By combining site-specific isotopic labeling (SSIL) and nuclear magnetic resonance (NMR), our group has succeeded to accurately analyze the cis-trans conformations of prolines present within the poly-proline tracts of huntingtin protein, the causative agent of Huntington's disease. Our data, recently published in the Journal of the American Chemical Society, show a strong influence of the neighboring residues on proline conformation. While the first proline of a poly-proline tract has a normal level of cis-conformation, prolines inside the tract are exclusively found in trans-conformation.